Epidermal Cells
The skin is the largest organ in the human body and consists of two components, the epidermis and the dermis. The dermis is a relatively inert structure which consists of collagen and other matrix materials. The epidermis lies above the dermis and is separated from it by a basement membrane.
The epidermis undergoes constant cell renewal and is regenerated approximately every 26 days. The major cellular constituent of the epidermis is the keratinocyte, which provides an environment for nonkeratinocytes (e.g., melanocytes, Langerhans cells, Merkel cells and various immunological cells) which also occur in the epidermis. Keratinocytes are cells which produce keratin, an insoluble fibrous protein, and are able to form a stratified squamous epithelia. Like other cells in the body, keratinocytes contain an entire complement of all genetic material. Only a small percentage of the genes contained in keratinocytes are, however, expressed at levels which are biologically functional; that is, most of the genes in keratinocytes are not expressed at all or are expressed at such low levels that the poplypeptides they encode are produced in undetectable amounts or concentrations which are biologically nonfunctional or insignificant. Like the epidermis, corneal epithelia and conjunctival epithelia are stratified squamous epithelia and the predominant cell in each of these tissues is the keratinocyte. Keratin is to a large degree responsible for the mechanical protective function of the epidermis. In addition, the epidermis acts as a barrier layer which prevents toxic substances and microorganisms from entering the skin and water and electrolytes from being lost.
The epidermis consists of two major layers. Outermost is the stratum corneum, which is a laminated layer of anucleate cornified cells. Next is a succession of viable inner cell layers, referred to as the malpighian layers from which the cornified cells arise. The malpighian layers are the basal cell layer, the stratum spinosum and the stratum granulosum. The basal cell layer, which lies adjacent to the basement membrane, is the germinative layer in which the majority of cell division occurs. The stratum spinosum is a layer of flattened nucleated cells having characteristic keratohyaline granules. The stratum granulosum lies between the stratum spinosum and the stratum corneum and is considered transitional between the nucleated cells of the former and the anucleate cells of the latter.
As the cells divide in the basal layer, they move upward and progress to the other epidermal layers. As they progress, the keratinocytes undergo changes in shape and cytoplasmic structure. These changes result in the viable, metabolically active cells being transformed into the anucleate, cornified cells of the horny layer; these cells consist of keratin filaments surrounded by a cross linked protein envelope. This progressive transformation is referred to as keratinization.
Epidermal cells are considered to occur in proliferative units or columns. The base of each column is a group of basal cells, which are classified as peripheral or central according to whether they lie beneath the periphery or the center of the column. The central basal cell divides; some of the resulting daughters in turn divide and move to peripheral basal positions. The peripheral basal cells then progress up through the successive epidermal layers. They are transformed into keratinized squamous cells, which ultimately flake off and are lost from the body. The central basal cells, however, are stem cells. Descendants of these stem cells will not die throughout the individual's lifetime. These basal cells are immortal and each time they divide, an immortal daughter cell results. The other daughter cells, as mentioned, become differentiating cells and are ultimately shed from the body. The epidermis is one of only a few tissues in the body which undergo constant cell renewal; these include other epithelia, such as the lining of the small intestine, and bone marrow.
It is possible, using methods developed in recent years to attain interspecies genetic recombination. Genes derived from totally different biological classes are able to replicate and be expressed in a selected microorganism. Therefore, it is possible to introduce into a microorganism genes specifying a metabolic or synthetic function (e.g., hormone synthesis, protein synthesis, nitrogen fixation) which is characteristic of other classes of organisms by linking the foreign genes to a particular viral or plasmid replicon.
Since the late 1970s, progress has been made toward the development of general methods for introducing cloned DNA sequences into mammalian cells. At the present time, however, there is a need for an effective method of introducing genetic material into epithelial cells and enable them to express genetic material which they do not usually express.